RN-1734

RN-1734 is a transient receptor potential vanilloid 4 (TRPV4) antagonist, blocking calcium influx induced by the TRPV4 agonist 4α-phorbol 12,13-didecanoate (Item No. 20446) with IC₅₀ values of 2.3, 5.9, and 3.2 µM for human, mouse, and rat TRPV4, respectively.¹ It is selective for TRPV4 over TRPV1, TRPV3, and TRPM8 (IC₅₀s = >100, >30, and >30 µM, respectively). RN-1734 (10 µM) reduces GSK1016790A-induced increases in glycine-activated current (I_Gly) from 34.5 to 0.97% in mouse hippocampal neurons in vitro.² It blocks arteriolar dilation induced by GSK1016790A (Item No. 17289) and increases myogenic tone in rat cremaster arterioles ex vivo when used at a concentration of 30 µM.³ RN-1734 (1 mg/kg, i.p.) reduces edema and MAPK signaling induced by traumatic brain injury in rats.⁴ It also inhibits breakdown of the blood-retinal barrier in streptozotocin-induced diabetic rats when administered at a dose of 100 µM.⁵

WARNING This product is not for human or veterinary use.

1. Vincent, F., Acevedo, A., Nguyen, M.T., et al. Identification and characterization of novel TRPV4 modulators. Biochem. Biophys. Res. Commun. 389(3), 490-494 (2009).

2. Qi, M., Wu, C., Wang, Z., et al. Transient receptor potential vanilloid 4 activation-induced increase in glycine-activated current in mouse hippocampal pyramidal neurons. Cell Physiol. Biochem. 45(3), 1084-1096 (2018).

3. Bagher, P., Beleznai, T., Kansui, Y., et al. Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca²⁺ events, and IKCa channels, reducing arteriolar tone. Proc. Natl. Acad. Sci. USA 109(44), 18174-18179 (2012).

4. Lu, K.-T., Huang, T.-C., Tsai, Y.-H., et al. Transient receptor potential vanilloid type 4 channels mediate Na^-K^-Cl-co-transporter-induced brain edema after traumatic brain injury. J. Neurochem. 140(5), 718-727 (2017).

5. Arredondo Zamarripa, D., Noguez Imm, R., Bautista Cortés, A.M., et al. Dual contribution of TRPV4 antagonism in the regulatory effect of vasoinhibins on blood-retinal barrier permeability: Diabetic milieu makes a difference. Sci. Rep. 7(1):13094, (2017).